The present research proposal outlines the continuation of our studies on familial neural atrophies and extends these to other disorders of lower motor and primary sensory neurons. In brief our objectives are: 1) to delineate further the natural history of disorders of lower motor and primary sensory neurons and especially of the inherited neuropathies; 2) to evaluate further which nerves are suitable for biopsy, the technique of biopsy and the symptoms from it; 3) to delineate further the normal anatomy of the nerves of man by histologic, histochemical, quantitative histologic and teased-fiber studies. Also to evaluate the quantitative histologic features and the light, phase and electron microscopic features of normal dorsal root ganglia at the S-1 level of man at various ages to be used as normative data; 4) to develop instruments for the quantitative measurement of touch-pressure, of discrimination of temperature differences and of pricking-pain threshold in health and in disorders of primary sensory neurons--to be correlated with the compound action potential and with numbers and spectrum of fibers; 5) to relate the quantitative histologic and teased fiber measurement and histologic abnormalities of nerve biopsies in various disorders of the primary sensory neuron to conduction velocity of nerves in vivo and in vitro and to EMG; 6) to study teased-fiber preparations and in cryostat and fixed sections by light, phase and electron microscopy the pathologic alteration of peripheral nerve (and, in a few highly selected cases, of more proximal portions of the same peripheral nerve and of the corresponding dorsal root ganglion) in various neuropathies of man and 7) to continue to evaluate systematically the biochemical changes in the peripheral nervous system which are characteristic of the inherited neuropathies. We wish to study further the systemic abnormality of ceramide hexosides and their sulphates which we have identified recently from a liver biopsy of a patient with hypertrophic neuropathy of the Dejerine-Sottas type. We intend to extend our study of biochemical profiles to include more patients with Dejerine-Sottas disease, more patients with peripheral neuropathies of other types, and more normal materials.